ELECTRON-TUNNELING PATHS IN VARIOUS ELECTROSTATIC COMPLEXES BETWEEN CYTOCHROME-C AND PLASTOCYANIN - ANISOTROPY OF THE COPPER LIGAND INTERACTIONS AND DEPENDENCE OF THE IRON COPPER ELECTRONIC COUPLING ON THE METALLOPROTEIN ORIENTATION

The Pathways method of Beratan and Onuchic is applied to analysis and comparison of electron-tunneling paths between the iron(II) and copper (II) sites in six configurations of the complex between ferrocytochrom e c and cupriplastocyanin. Standard parametrization is used, and elect ronic coupling in aromatic rings is treated as both attenuated and una ttenuated; the results did not significantly depend on this choice. In one methodological improvement, crystallographically detected water m olecules are included inside the proteins, and the vicinity of the pro tein-protein interface is hydrated in a molecular simulation. in anoth er improvement, anisotropy of metal-ligand electronic coupling in the blue copper site is explicitly recognized. Standard calculations, in w hich the copper(II)-ligand coupling is treated as isotropic. showed th e so-called northern equatorial configuration to have the greatest iro n(II)-copper(II) coupling, i.e., the best tunneling paths. Other confi gurations provide neither few excellent paths nor many good ones. Scal ed calculations, in which the anisotropy of the copper(II)-ligand coup ling is treated in three different ways, favor the paths ending with C ys 84 and disfavor or abolish those ending with the other three ligand s. These scaled calculations consistently showed the northern equatori al and the so-called ''maximum-overlap, rotated'' configurations to ha ve greater coupling than the other electrostatically-stabilized config urations of the diprotein complex. The so-called maximum-overlap confi guration, which has optimal electrostatic docking, lags behind the oth er two configurations in electronic coupling. Calculations of electron ic coupling of the iron(II) and copper(II) sites to the surfaces of th e respective proteins and matching of the surface patches in the two p roteins were consistent with the analysis of iron(II)-copper(II) coupl ings. There are steric obstacles to contacts between the ''conductive' ' surface patches in the maximum-overlap configuration but not in the northern equatorial configuration. This theoretical study corroborates experimental findings in this laboratory that the diprotein complex w ith optimal electrostatic interactions is not optimal for the intracom plex electron-transfer reactions. In studies of metalloprotein complex es by the Pathways method, internal and external hydration, anisotropy of metal-ligand coupling, and steric effects should all be considered .